Exercise Interventions Incorporating Aerobic Components in Children and Adolescents with Acute Lymphoblastic Leukemia: A Systematic Review and Meta-Analysis

Background: Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. Despite substantial improvements in survival, children and adolescents with ALL frequently experience treatment-related impairments in physical function, mobility, and quality of life. Exercise interventions incorporating aerobic components have been proposed as supportive rehabilitation strategies to mitigate these sequelae. Objective: This study aimed to evaluate the effects of exercise interventions containing aerobic components as adjuncts to standard treatment on quality of life and related functional outcomes in children and adolescents with ALL. Methods: This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and prospectively registered in PROSPERO (CRD42024581010). MEDLINE (via PubMed), Web of Science, and Scopus were searched from inception to April 2026. The Cochrane Central Register of Controlled Trials (CENTRAL), ClinicalTrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform (WHO ICTRP) were additionally searched on 3 October 2026. Randomized controlled trials evaluating structured exercise interventions with an aerobic component in children and adolescents with ALL were included. The primary outcome was quality of life. Secondary outcomes included functional mobility, functional capacity, and related physical performance outcomes. Random-effects meta-analyses were performed when appropriate, and certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Results: Five randomized controlled trials involving 254 participants met the inclusion criteria. Interventions consisted of supervised or home-based exercise programs incorporating aerobic activities in combination with other rehabilitation modalities. Meta-analysis suggested improvements in functional mobility and functional capacity compared with control interventions (low-certainty evidence). Quality-of-life findings were inconsistent across studies and were not suitable for quantitative pooling because of heterogeneity in instruments, reporting methods, and outcome domains; the certainty of evidence was rated as very low. No serious exercise-related adverse events were reported, although safety monitoring was inconsistently described. Conclusions: The effects of exercise interventions containing aerobic components on quality of life in children and adolescents with ALL remain very uncertain. Low-certainty evidence suggests that these interventions may improve functional mobility and functional capacity. Additional adequately powered, methodologically rigorous randomized controlled trials with standardized outcome measures, predefined adverse-event reporting, and comprehensive safety monitoring are required to establish the effectiveness and safety of these interventions in pediatric oncology rehabilitation.